Search

Decellularized tissue-engineered constructs have the potential to promote regeneration by providing a biomimetic extracellular matrix that directs tissue-specific regeneration when implanted in situ. Recently, the use of cell sheets has shown promising results in promoting periodontal regeneration. Here, we describe the fabrication of decellularized periodontal cell sheets with intact extracellular matrix structural and biological properties. Melt electro spun polycaprolactone (PCL) scaffolds are used as a carrier for the inherently fragile cell sheets, to provide support during the processes of decellularization. An optimized decellularization method is outlined using perfusion with a combination of NH4OH and Triton X-100 together with a DNase treatment step for DNA removal. The maintenance of extracellular matrix structural and biological integrity is important, and here we describe the assessment of these properties using immunostaining for extracellular matrix proteins and ELISA for growth factor quantification.

Decellularized tissue engineered constructs have the potential to promote regeneration by providing a biomimetic extracellular matrix that directs tissue specific regeneration when implanted in situ. Recently, the use of cell sheets has shown promising results in promoting periodontal regeneration. Here, we describe the fabrication of decellularized periodontal cell sheets with intact extracellular matrix structural and biological properties. Melt electro-spun polycaprolactone (PCL) scaffolds are used as a carrier for the inherently fragile cell sheets, in order to provide support during the processes of decellularization. An optimized decellularization method is outlined using perfusion with a combination of NH

Objectives P4 Medicine is based on a proactive approach for clinical patient care incorporating the four “pillars” of prediction, prevention, personalization, and participation for patient management. The purpose of this review is to demonstrate how the concepts of P4 medicine can be incorporated into the management of periodontal diseases (particularly periodontitis) termed P4 periodontics. Methods This is a narrative review that used current literature to explore how P4 periodontics can be aligned with the 2018 Classification of Periodontal Diseases, current periodontal treatment paradigms, and periodontal regenerative technologies. Results The proposed model of P4 periodontics is highly aligned with the 2018 Classification of Periodontal Diseases and represents a logical extension of this classification into treatment paradigms. Each stage of periodontitis can be related to a holistic approach to clinical management. The role of “big data” in future P4 periodontics is discussed and the concepts of a treat-to-target focus for treatment outcomes are proposed as part of personalized periodontics. Personalized regenerative and rejuvenative periodontal therapies will refocus our thinking from risk management to regenerative solutions to manage the effects of disease and aging. Conclusions P4 Periodontics allows us to focus not only on early prevention and intervention but also allow for personalized late-stage reversal of the disease trajectory and the use of personalized regenerative procedures to reconstruct damaged tissues and restore them to health. Clinical Significance P4 Periodontics is a novel means of viewing a holistic, integrative, and proactive approach to periodontal treatment.

Background and Aims: To describe the biology of alveolar bone regeneration.Material and Methods: Four comprehensive reviews were performed on (a) mesenchymal cells and differentiation factors leadi ...

This study investigated changes induced by Porphyromonas gingivalis and on gastrointestinal histology and gut microbiome in a mouse model of experimental periodontitis. The effect of probiotic Lactobacillus rhamnosus GG (LGG) in altering these changes was also investigated.IThirty-six mice were allocated into six groups. Experimental alveolar bone loss was induced by oral inoculation with P. gingivalis and F. nucleatum. LGG was orally inoculated or orally gavaged. Gastrointestinal tissue changes were assessed using histological analysis and immunohistochemistry. Caecal microbiome was analysed by sequencing 16S rRNA genes of caecal content.Inoculation with P. gingivalis and F. nucleatum induced inflammation throughout gastrointestinal tract (p less than 0.05), increased expression of IL-6 in ileum (p = 0.052) and altered composition of caecal microbiome (p less than 0.05) in experimental mice compared to controls. Mice treated with LGG had reduced tissue inflammation in duodenum (p = 0.044) and lowered levels of IL-6 in ileum (p = 0.048) when compared with disease. LGG therapy influenced gut microbiome changes.P. gingivalis and F. nucleatum inoculation induced significant changes in intestinal inflammation and caecal microbiome. Oral gavage with LGG exerted a protective effect against intestinal inflammation and limited gut microbiome changes associated with P. gingivalis and F. nucleatum.

Drug use for both therapeutic and recreational purposes is very widespread in most societies. The range of drugs used, the variations in response to these drugs and other health and behavioral confounders mean that drug use may be an important contributor to individualized periodontal diagnoses. In this narrative review, we review the main reported effects of drugs on the periodontal tissues and periodontal disease processes. Although some of the more common adverse drug reactions on periodontal tissues are well described, in many other cases the evidence for these drug effects is quite limited and based on small case series or isolated reports. Prescription drugs are responsible for a range of effects, including drug-induced gingival overgrowth and increased gingival bleeding, and influence periodontal inflammation and periodontal breakdown. The effects of recreational drugs on the periodontal tissues is less well researched, perhaps for the obvious reason that assembling large cohorts of recreational drug users presents particular challenges. Use of nearly all of these substances is associated with poorer periodontal and dental health, although there is almost certainly a large degree of behavioral confounding in these findings. Overall, further studies of adverse drug reactions on the periodontal tissues are required as this continues to be an important and increasing factor in periodontal health determination.

Personalized medicine is a medical model that involves the tailoring of healthcare - with medical decisions, practices, and/or products being customized to an individual patient. In this model, diagnostic testing is often employed for selecting appropriate and optimal therapies based on the context of a patient's genetic content or other epidemiologic, sociologic, molecular, physiologic, or cellular analyses. With the advent of major advances in periodontal medicine, including genomic discoveries and greater understanding of the multifactorial nature of periodontitis, it seems that the time is ripe to use personalized medicine as a model for personalized periodontics. This volume of Periodontology 2000 explores how new advances in our understanding of periodontitis within a medical model can evolve into new treatment strategies tailor-made for individual patients and not merely based on wholesale treatment paradigms.

Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non-periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non-dental plaque biofilm-induced gingival diseases and dental plaque-induced gingivitis. Non-dental plaque biofilm-induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque-induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque-induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non-periodontitis patient or in a currently stable "periodontitis patient" i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient-centered approach to care, and therefore, creates differences in the way in which a "case" of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations. ispartof: JOURNAL OF PERIODONTOLOGY vol:89 pages:S74-S84 ispartof: location:IL, Chicago status: published

To date there is a paucity of documentation regarding definitions of periodontal health. This review considers the histological and clinical determinants of periodontal health for both intact and reduced periodontium and seeks to propose appropriate definitions according to treatment outcomes.Defining periodontal health is can serve as a vital common reference point for assessing disease and determining meaningful treatment outcomes.The multifactorial nature of periodontitis is accepted, and it is recognized that restoration of periodontal health will be defined by an individual's response to treatment, taking into account allostatic conditions.It is proposed that there are 4 levels of periodontal health, depending on the state of the periodontium (structurally and clinically sound or reduced) and the relative treatment outcomes: (1) pristine periodontal health, with a structurally sound and uninflamed periodontium; (2) well-maintained clinical periodontal health, with a structurally and clinically sound (intact) periodontium; (3) periodontal disease stability, with a reduced periodontium, and (4) periodontal disease remission/control, with a reduced periodontium.

Purpose of Review Periodontal medicine recognizes a “bidirectional” interaction between periodontitis and systemic conditions. Unfortunately, the facile ability to publish a periodontal-systemic association, regardless of biologic plausibility or rigorous scientific scrutiny, continues without abate. Recent Findings The increasing number of periodontal-systemic associations corrupts the ability of dentists to distinguish which of the associations are spurious and which are valid. Summary The use of a Disease Association Checklist creates a register for rational assessment of current disease associations. However, to diminish the publication of spurious periodontal-systemic observational associations, editors must demand that authors follow Bradford-Hill criteria and the STROBE Statement to ensure a stringent pathway to publication.

This review was designed to explore the use of probiotics in prevention or treatment of periodontitis.A search was performed using MEDLINE and bibliographies from previous reviews in order to identify any randomised controlled animal and human probiotic interventions in periodontitis.Five studies using probiotics in animal models of periodontitis and eight clinical studies using probiotics in patients with chronic periodontitis were analysed. The analysis of the animal models showed reduction in periodontal pathogens and bleeding on probing when probiotics were used in adjunction to mechanical debridement and significant increase in alveolar bone levels and bone density in the probiotic groups when compared with placebo. Some of the results of the clinical studies indicated decreased clinical parameters (gingival inflammation, bleeding on probing, plaque index) and decreased pro-inflammatory markers levels in saliva or gingival crevicular fluid in treated periodontitis patients when compared with controls or placebo. Other results included decreased periodontal pocket depth and clinical attachment loss for scaling and root planing plus probiotic treatment versus scaling and root planing alone or placebo and also reduction in Porphyromonas gingivalis numbers and the total viable count and proportion of obligate anaerobic bacteria.Within the limitations of this review, the results are encouraging, supporting the notion that there is a place for probiotics in the treatment of periodontitis. Future independent studies are needed to investigate specific probiotic strains, doses, delivery methods, treatment schedules, mechanisms of action, safety and how to maintain the results of the probiotic interventions.

The 1st International Academy of Periodontology Research Conference (IAPRC) was successfully held in Giessen, Germany from October 2-4. The objectives of the IAPRC were: to examine the state of the art in periodontal research, to encourage new scientific collaborations and to develop new directions for research.

To assess the impact of extent and severity of chronic periodontitis (CP) on oral health-related quality of life (OHRQoL).A cross-sectional comparative study was performed on subjects from multiple dental centres in Malaysia using a questionnaire covering sociodemographics, OHRQoL using the Malaysian Oral Health Impact Profile questionnaire, OHIP-14(M) and self-reported symptoms. Participants with severe CP were age-and gender-matched with periodontally healthy/mild periodontitis (HMP) participants based on inclusion and exclusion criteria. Full mouth periodontal examination was performed on participants. Outcome measures were OHIP-14(M) prevalence of impact and severity of impact scores.One hundred and thirty (130) participants comprising 65 severe CP and 65 HMP participants were included in the study. Prevalence of impact on OHRQoL was significantly higher in the severe CP than HMP group, with an odds ratio of 3. Mean OHIP-14(M) score was significantly higher in the severe CP (18.26 ± 10.22) compared to HMP (11.28± 8.09) group. The dimensions of psychological discomfort and functional limitation, and factors such as 'discomfort due to food stuck' and 'felt shy' were impacted more in severe CP compared to HMP group (p0.05). When compared with the HMP group, generalised severe CP participants showed higher prevalence of impact on OHRQoL [OR=5] (p0.05) compared to localised severe CP [OR=2] (p = 0.05). Participants who had experienced self-reported symptoms had statistically significant impacts on OHRQoL.Severe CP had a greater impact on OHRQoL compared to HMP. Impacts were mainly for functional limitation and psychological discomfort dimensions. When considering extent of disease, the impact on OHRQoL was mostly in generalised severe CP subgroup.

To describe the biology of alveolar bone regeneration.Four comprehensive reviews were performed on (a) mesenchymal cells and differentiation factors leading to bone formation; (b) the critical interplay between bone resorbing and formative cells; (c) the role of osteoimmunology in the formation and maintenance of alveolar bone; and (d) the self-regenerative capacity following bone injury or tooth extraction were prepared prior to the workshop.This summary information adds to the fuller understanding of the alveolar bone regenerative response with implications to reconstructive procedures for patient oral rehabilitation. The group collectively formulated and addressed critical questions based on each of the reviews in this consensus report to advance the field. The report concludes with identified areas of future research.

The ultimate goal of periodontal treatment is not only the stabilization of periodontal disease but also regeneration of the periodontal tissues destroyed by severe periodontitis. The tissue engineering triad of stem cells, biological signals, and cell-seeded scaffold provides a biological template for tissue regeneration. Neural crest stem cells (NCSC) comprise a transient multipotent stem cell population that initially emerges from the junction of the epidermal and neural ectoderm through reciprocal interactions between these tissues and signals from the mesoderm during embryonic development of vertebrates. The cells then migrate to their destination in the embryo and differentiate into various dental mesenchymal stem cells which give rise to most components of the dental tissues, including periodontal ligament (PDL), alveolar bone, cementum, dental pulp, and dentin. The crucial role that NCSC play in embryonic development makes them a highly promising stem cell population for use in the regeneration of periodontal tissues. Here, we review the current understanding of the features and functions of NCSC-derived cells in dental tissues. We additionally discuss the possibility that NCSC contribute to the regeneration of periodontal tissues.

Periodontitis, a major chronic inflammatory disease of dental tissue, causes periodontal tissue destruction and alveolar bone resorption. When large amounts of alveolar bone are lost, it is very difficult to regenerate the bone using conventional treatments. Periodontal ligament stem cells (PDLSCs) have attracted much attention as potential cell sources for alternative periodontitis regenerative treatment because of their capacity for self-renewal and multipotency. Recently, PDLSCs were found to possess immunomodulatory properties. PDLSCs lack the expression of immune co-stimulating factors and suppress immune cell proliferation following stimulation with mitogens or in mixed allogeneic lymphocyte reactions. Because of these characteristics, the anti-inflammatory effects of PDLSCs and the establishment of allogeneic PDLSC transplantation therapies have been well studied. The aim of this review is to provide an assessment of the latest findings on the immunomodulatory properties of PDLSCs and their potential clinical application for periodontal tissue regeneration.

Histone deacetylase 1 (HDAC1) is highly expressed in the synovium of RA patients. Thus we aimed to investigate a novel HDAC inhibitor (HDACi), NW-21, designed to target HDAC1. The effect of NW-21 on osteoclast formation and activity, cytokine and chemokine expression in vitro and arthritis in mice was assessed.The effects on human osteoclast formation and activity derived from human blood monocytes stimulated with receptor activator of nuclear factor κB ligand (RANKL) and M-CSF were assessed. The anti-inflammatory activity of NW-21 was assessed using human monocytes stimulated with either TNF-α or lipopolysaccharide for 24 h. mRNA expression of monocyte chemotactic protein 1 (MCP-1), TNF-α, macrophage inflammatory protein 1α (MIP-1α), IL-1 and RANTES (regulated on activation, normal T cell expressed and secreted) was assessed. The effect of NW-21 in the collagen antibody-induced arthritis model was assessed following daily oral administration at 5 mg/kg/day. The HDAC1 inhibitors NW-21 and MS-275 were compared with a broad-acting HDACi, 1179.4b. Effects on inflammation and bone were assessed using paw inflammation scoring, histology and live animal micro-CT.NW-21 suppressed osteoclast formation and activity as well as significantly reducing mRNA expression of MCP-1 and MIP-1α in monocytes stimulated by lipopolysaccharide or TNF-α (P0.05) in vitro. Only inhibitors that targeted HDAC1 (NW-21 and MS-275) reduced inflammation and bone loss in the arthritis model.The results indicate that inhibitors targeting HDAC1, such as NW-21 and MS-275, may be useful for treating RA, as such drugs can simultaneously target both inflammation and bone resorption.

Historically, periodontal disease (gingivitis and periodontitis) has been recognized as being primarily of bacterial origin. However, recent evidence indicates that while bacteria are necessary for disease development they are not sufficient for the clinical manifestation of the many and varied forms of periodontal disease. It is becoming increasingly apparent that it is the host inflammatory response to the subgingival bacteria that is responsible for the tissue damage and, most likely, progression of the disease. We explore the concept that it is the subgingival microenvironment modified by the inflammatory response that leads to a change from a commensal to pathogenic microbiota. In this review, we examine the evidence for the emerging paradigm supporting the central role of inflammation rather than specific microbiota in the pathogenesis of periodontitis, and that by controlling the inflammation, it is possible to control the infection. As an extension of this, we propose a working model for the ongoing monitoring of periodontal patients using the medical model of 'treat to target'.

Objective Periodontitis is a potential risk factor for rheumatoid arthritis (RA). This systematic review considers the evidence for whether non-surgical treatment of periodontitis in RA patients has any effect on the clinical markers of RA disease activity. Methods MEDLINE/PubMed, CINAHL, DOSS, Embase, Scopus, Web of Knowledge, MedNar, Lilacs and ProQuest Theses and Dissertations were searched till September 2013 for quantitative studies examining the effect of non-surgical periodontal treatment on disease activity of RA. The following were the inclusion criteria: (1) patients diagnosed with both RA and chronic periodontitis, aged 30 years or older; (2) no antibiotics in the past 3 months or periodontal treatment in the past 6 months; (3) non-surgical periodontal therapy; (4) age- and gender-matched control group; (5) measures of RA activity and (6) published in English. Results Five studies met the inclusion criteria. Non-surgical periodontal treatment was associated with significant reductions in erythrocyte sedimentation rate and a trend towards a reduction in TNF-α titres and DAS scores. There was no evidence of an effect on RF, C-reactive protein, anti-cyclic citrullinated protein antibodies and IL-6. Conclusions Based on clinical and biochemical markers, non-surgical periodontal treatment in individuals with periodontitis and RA could lead to improvements in markers of disease activity in RA. All studies had low subject numbers with the periods of intervention no longer than 6 months. Larger studies are required to explore the effect of non-surgical periodontal treatment on clinical indicators of RA, using more rigorous biochemical and clinical outcome measures as well as giving consideration to potential confounding factors of co-morbidity.

The therapeutic potential of mesenchymal stem cells (MSC) has highlighted the need for identifying easily accessible and reliable sources of these cells. An alternative source for obtaining large populations of MSC is through the controlled differentiation of induced pluripotent stem cells (iPSC). In the present study, colonies of iPSC were cultured in MSC culture media for 2 weeks. Serial passaging then selected for fast growing MSC-like cells with a typical fibroblastic morphology and the capacity to proliferate on standard culture flasks without feeder cells. MSC-like cells were developed from iPSC lines arising from three different somatic tissues: gingiva, periodontal ligament (PDL), and lung. The iPSC-MSC like cells expressed key MSC-associated markers (CD73, CD90, CD105, CD146, and CD166) and lacked expression of pluripotent markers (TRA160, TRA181, and alkaline phosphatase) and hematopoietic markers (CD14, CD34, and CD45). In vitro iPSC-MSC-like cells displayed the capacity to differentiate into osteoblasts, adipocytes, and chondrocytes. In vivo subcutaneous implantation of the iPSC-MSC-like cells into NOD/SCID mice demonstrated that only the PDL-derived iPSC-MSC-like cells exhibited the capacity to form mature mineralized structures which were histologically similar to mature bone. These findings demonstrate that controlled induction of iPSC into fibroblastic-like cells that phenotypically and functionally resemble adult MSC is an attractive approach to obtain a readily available source of progenitor cells for orthopedic and dental-related tissue-engineering applications. However, a detailed characterization of the iPSC-MSC-like cells will be important, as MSC-like cells derived from different iPSC lines exhibit variability in their differentiation capacity Refereed/Peer-reviewed

Periodontitis and radiation-induced oral mucositis are both inflammatory conditions which may be associated through a common underlying dysregulation of the inflammatory response. This pilot study aimed to determine whether the severity of oral mucositis is associated with the severity of periodontitis in cancer patients undergoing head and neck radiotherapy. In this pilot study, 41 patients met the inclusion criteria. The severity of oral mucositis was measured according to the WHO system. The severity of periodontitis was assessed clinically and radiographically. Gingival crevicular fluid was sampled and levels of eight cytokines were determined using a multiplexed bead immunoassay. Associations between radiation-induced oral mucositis and periodontitis were analysed using logistic and linear regression. There was a trend towards a greater proportion of periodontitis patients in the mucositis groups (grades = 1–4) than in the non-mucositis group (grade = 0). However, due to the small sample size of this pilot study, these trends were not statistically significant. This pilot study did not demonstrate a positive statistical correlation between periodontitis experience and severity of radiation-induced oral mucositis. Nonetheless, a trend towards increased bone loss, pocket depth and clinical attachment levels was noted in patients with mucositis grades 1–4. Larger studies with more stringent inclusion criteria are now required to further investigate this possible relationship between periodontitis experience and severity of radiation-induced oral mucositis.

The realisation that adult somatic cells can be reprogrammed into pluripotent cells is revolutionising the way diseases are researched and is set to transform the way diseases are treated. In recent years the use of induced pluripotent stem cells (iPSC) in dentistry has begun to be investigated. Whilst this work is still in its infancy, iPSC are demonstrating great potential for use in the regeneration of dental tissues. In this review we will provide a brief introduction to the properties of iPSC and their potential application as therapeutic agents to enhance medical research. Furthermore, this review will summarise recent developments in the use of iPSC in dental tissue regeneration.

Aim: To investigate the capacity of allogeneic periodontal ligament stem cells (PDLSCs) to regenerate periodontal tissues using an ovine periodontal defect model. Materials & methods: Surgically created zero-wall dehiscence periodontal defects created in Merino sheep were filled with 1 × 107 allogeneic PDLSCs attached to Gelfoam®, Gelfoam alone or left untreated. After 4 weeks, histological analysis was performed to assess periodontal regeneration. Results: Allogeneic PDLSCs were well tolerated by recipient animals. The mean area of new alveolar bone was significantly greater in the PDLSC + Gelfoam treatment group compared with the defect-alone group. The PDLSC + Gelfoam and Gelfoam-only treatment groups displayed significantly greater length of new cementum and percentage of cementum regrowth compared with the defect-alone group. New Sharpey‘s fibers were generally more organized and significantly thicker within the PDLSC + Gelfoam treatment group. The PDLSC + Gelfoam treatment group also showed a trend of increased Sharpey‘s fiber attachment length compared with the Gelfoam-only and defect-alone groups. Conclusion: These studies support the potential use of allogeneic PDLSC preparations as viable therapies for periodontal regeneration in the clinical setting.

Periodontitis is a highly prevalent inflammatory disease that results in damage to the tooth-supporting tissues, potentially leading to tooth loss. Periodontal tissue regeneration is a complex process that involves the collaboration of two hard tissues (cementum and alveolar bone) and two soft tissues (gingiva and periodontal ligament). To date, no periodontal-regenerative procedures provide predictable clinical outcomes. To understand the rational basis of regenerative procedures, a better understanding of the events associated with the formation of periodontal components will help to establish reliable strategies for clinical practice. An important aspect of this is the role of the Hertwig's epithelial root sheath in periodontal development and that of its descendants, the epithelial cell rests of Malassez, in the maintenance of the periodontium. An important structure during tooth root development, the Hertwig's epithelial root sheath is not only a barrier between the dental follicle and dental papilla cells but is also involved in determining the shape, size and number of roots and in the development of dentin and cementum, and may act as a source of mesenchymal progenitor cells for cementoblasts. In adulthood, the epithelial cell rests of Malassez are the only odontogenic epithelial population in the periodontal ligament. Although there is no general agreement on the functions of the epithelial cell rests of Malassez, accumulating evidence suggests that the putative roles of the epithelial cell rests of Malassez in adult periodontal ligament include maintaining periodontal ligament homeostasis to prevent ankylosis and maintain periodontal ligament space, to prevent root resorption, to serve as a target during periodontal ligament innervation and to contribute to cementum repair. Recently, ovine epithelial cell rests of Malassez cells have been shown to harbor clonogenic epithelial stem-cell populations that demonstrate similar properties to mesenchymal stromal/stem cells, both functionally and phenotypically. Therefore, the epithelial cell rests of Malassez, rather than being 'cell rests', as indicated by their name, are an important source of stem cells that might play a pivotal role in periodontal regeneration.

The periodontium is a very dynamic organ that responds rapidly to mechanical and chemical stimuli. It is very complex in that it is composed of two hard tissues (cementum and bone) and two soft connective tissues (periodontal ligament and gingiva). Together these tissues are defined by the molecules expressed by the resident periodontal cells in each compartment and this determines not only the structure and function of the periodontium but also how it responds to infection and inflammation. The biological activity of these molecules is tightly regulated in time and space to preserve tissue homeostasis, influence inflammatory responses and participate in tissue regeneration. In this issue of Periodontology 2000 we explore new experimental approaches and data sets which help to understand the molecules and cells that regulate tissue form and structure in health, disease and regeneration.

New paradigms emerge when existing ones fail to address known factors adequately or are invalidated by new evidence. In this paper, we explore some long-held tenets in the pathogenesis of periodontitis and, in light of emerging data and concepts, challenge their validity. For decades periodontitis has been considered to be caused by specific bacteria or groups of bacteria and, accordingly, treatment protocols have been based largely on anti-infective therapies. However, close inspection of the available data leads one to question whether overgrowth of bacteria is the cause or the result of periodontitis. Over the same decades considerable evidence was presented which indicated that it is more likely to be the host response to the bacteria that leads to the tissue changes noted in gingivitis and periodontitis. Thus, it seems that it is the host inflammatory and immune responses, and not specific bacteria or their ‘putative’ virulence factors, which determine whether periodontitis develops and progresses. In this review, we highlight aspects of the pathogenesis of periodontitis that we suggest should be re-evaluated in light of the current evidence and discuss emerging treatment paradigms. No longer should the tissue changes noted in this classic chronic inflammatory condition be considered to be solely of microbial origin. In this review, we explore the evidence for a role of bacteria in the initiation, progression and treatment of periodontitis. The title of this review is a rewording of a recent paper entitled ‘Periodontitis: a polymicrobial disruption of host homeostasis’ (21). We present this title in the context of unlearning learned concepts in periodontics and the need for a significant re-evaluation of our understanding of the pathogenesis of periodontitis.

The periodontium is composed of the tissues supporting and investing the tooth. One of the major goals of periodontal therapy is to encourage regeneration of tissues that have been destroyed as a result of periodontal disease. Bone grafting materials have been used to replace the alveolar bone lost within the periodontal defect, with the rationale being that this would facilitate new attachment formation to the adjacent root surface. Guided tissue regeneration (GTR) uses biocompatible barrier membranes to enable selective cellular recolonisation of periodontal defects. For successful periodontal regeneration via tissue engineering, the engineered tissues should have sufficient biomechanical strength, architectural properties, and space-maintaining ability. Several preclinical trials have shown that bone marrow-derived mesenchymal stem cells (BMMSCs) have the capacity to promote periodontal regeneration through enhanced generation of cementum, periodontal ligament, alveolar bone, and neovascularisation. The use of decellularised matrices as a biologic scaffold is gaining increasing attention in regenerative medicine.

Purpose: The aim of this systematic review was to evaluate current and emerging regenerative approaches for implant site development in the edentulous atrophic maxilla using tissue engineering and regenerative medicine (TERM) principles and to identify priorities for future research. Materials and Methods: Two independent examiners conducted a comprehensive search using specific keywords to identify original clinical studies using TERM for implant site development in the edentulous atrophic maxilla including indications for alveolar ridge preservation, horizontal alveolar augmentation, maxillary sinus augmentation, and augmentation of severe vertical or combined defects. Endpoints included clinical, radiographic, histologic, and patient-centered outcomes. Results: The initial search identified 3,061 articles. The final selection included 89 articles, of which 12 evaluated alveolar ridge preservation, 6 horizontal defects, 61 maxillary sinus augmentation, and 11 management of severe vertical or combined defects. A summary of the main findings relative to the effect of TERM-based approaches applied for implant site development in the atrophic maxillary segments is presented. Marked heterogeneity among included studies prevented meaningful quantitative analysis. The following relevant effects of TERM-based therapies for site development in the edentulous atrophic maxilla were observed: (1) recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier increased bone augmentation; (2) recombinant human platelet-derived growth factor BB in combination with freeze-dried bone allograft or beta tricalcium phosphate accelerated bone formation through accelerated remodeling of carrier biomaterials; (3) autologous cell therapy enhanced clinical and radiographic outcomes; (4) autologous cell therapy in alveolar ridge preservation provided superior histomorphometric outcomes (vital bone formation) at 6 weeks; and (5) platelet-rich plasma formulations combined with autologous bone grafts for maxillary sinus augmentation increased radiographic density and accelerated bone mineralization at 6 months. Conclusion: Clinical success has been demonstrated with the application of different TERM modalities for implant site development in the edentulous atrophic maxilla. However, indications are narrow and further study is needed. Clinical trials assessing meaningful outcomes, involving larger populations, and with longer follow-up are warranted to discern the effectiveness of the achieved results compared with a valid control.

Objectives To provide a metallurgical and histomorphological analysis of hybrid bridgework and associated dental implants which have been in a clinical load bearing situation for a period of 12.5 years. Material and methods The physical integrity of the hybrid framework was examined with stereoimaging microscopy and scanning electron microscopy for signs of wear, fatigue cracks, corrosion. Elemental spectra and maps of the surface were analysed with an EDAX® Detecting Unit (AMETEK, Inc, Mahwah, NJ, USA). Similarly, the supporting titanium abutments screwed into the implants were examined for fatigue and corrosion. Bone density scans and bone trabecular patterns were obtained from radiographs. Microcomputer tomography was used to assess the bone–implant interface and bone architecture around the implants. Histological sections were stained with 1% basic fuchsin to assess osseous microdamage. Results The study demonstrated that the gold alloy framework to be in satisfactory condition with little indication of corrosion or cracking. The interface between the gold alloy and the titanium abutments likewise demonstrated no obvious corrosion cells. No radiographic evidence of any adverse loss of bone around the implants was noted. Bone mineral density was related to implant position, being higher between the implants. Scanning electron micrograph images confirmed the good bone integration with the implant threads with a high level of organisation, maturation and adaptation for the entire length of the implant. There was no evidence of any microdamage. Conclusions The implants, abutments and hybrid framework were in remarkably good condition considering their length of service.

Objectives The aim of this investigation was to examine the effect of a combination of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (β-TCP) on bone healing around dental implants with critical size circumferential defects. Material and methods Three critical size circumferential defects were prepared in the ilium of six sheep. Three dental implants were placed into the centre of each defect and the 3.25 mm circumferential gap was filled with (a) blood clot alone; (b) β-TCP; (c) rhPDGF-BB (0.3 mg/ml) with β-TCP. All the defects in each group were covered with a Bio-Gide® resorbable barrier membrane. The sheep were sacrificed at 2 and 4 weeks and histological and histomorphometric analyses were performed to determine the percentage of new mineralized bone formation and residual β-TCP graft particles in the defects. Results Defects filled with rhPDGF-BB/β-TCP showed the highest rate of bone formation after 2 and 4 weeks with limited degradation of the β-TCP particles over 4 weeks. Defects filled with β-TCP showed the least bone fill after 2 and 4 weeks, and faster degradation of the β-TCP particles over 4 weeks compared with defects filled with rhPDGF-BB/β-TCP. Percentage of new mineralized bone was comparable in defects to blood clot alone and β-TCP after 4 weeks of healing, but there was a collapse in the defect area in defects with blood clot alone. In comparison, the space was maintained when β-TCP was used in defects at 4 weeks. Conclusions Defects which had β-TCP alone showed an inhibition in bone healing at 2 and 4 weeks; however, the combination of rhPDGF-BB with β-TCP enhanced bone regeneration in these peri-implant bone defects at the same time intervals.